Targeting MYC-driven replication stress in medulloblastoma with AZD1775 and gemcitabine

Journal of Neuro-Oncology - MYC-driven medulloblastomas are highly aggressive childhood tumors with dismal outcomes and a lack of new treatment paradigms. We identified that targeting replication...     

Charge transport and rectification in molecular junctions formed with carbon-based electrodes

Molecular junctions formed using the scanning-tunneling-microscope–based break-junction technique (STM-BJ) have provided unique insight into charge transport at the nanoscale. In most prior work, the same metal, typically Au, Pt, or Ag, is used for both tip and substrate. For such noble metal electrodes, the density of electronic states is approximately constant within a narrow energy window relevant to charge transport. Here, we form molecular junctions using the STM-BJ technique, with an Au metal tip and a microfabricated graphite substrate, and measure the conductance of a series of graphite/amine-terminated oligophenyl/Au molecular junctions. The remarkable mechanical strength of graphite and the single-crystal properties of our substrates allow measurements over few thousand junctions without any change in the surface properties. We show that conductance decays exponentially with molecular backbone length with a decay constant that is essentially the same as that for measurements with two Au electrodes. More importantly, despite the inherent symmetry of the oligophenylamines, we observe rectification in these junctions. State-of-art ab initio conductance calculations are in good agreement with experiment, and explain the rectification. We show that the highly energy-dependent graphite density of states contributes variations in transmission that, when coupled with an asymmetric voltage drop across the junction, leads to the observed rectification. Together, our measurements and calculations show how functionality may emerge from hybrid molecular-scale devices purposefully designed with different electrodes beyond the so-called “wide band limit,” opening up the possibility of assembling molecular junctions with dissimilar electrodes using layered 2D materials.Recent interest in understanding charge transport in molecular-scale devices and at metal/organic interfaces has led to innovations in both experimental and theoretical techniques designed to probe such devices (1, 2). Molecular junctions in a metal–molecule–metal motif using a variety of metals including Au, Ag, Pt, Al, and Cu have been studied extensively (3–7), contributing significantly to our understanding of the fundamental principles required to realize molecular-scale electronic components such as rectifiers or switches (8–14). However, the nanogap electrodes using such metals are mechanically unstable due to the high atomic mobility of metal atoms (15–18) and all except for Au oxidize easily under ambient conditions (6). Furthermore, the electrode density of states near the Fermi energy is typically nearly energy independent. This results in molecular junctions formed with metals having rather smooth and featureless transmission probabilities around the Fermi energy, limiting their applications. Carbon-based electrodes such as graphite have remarkable mechanical strength as well as a nonconstant highly dispersive density of states near its Fermi energy (19). In addition, molecules can be bonded covalently to carbon-based materials and can also bind through a van der Waals-based π–π stacking interaction (20). However, to date, such materials have not been used to create molecular junctions using the scanning-tunneling-microscope–based break-junction technique (STM-BJ). All-carbon electrodes have been used in the past, including carbon nanotubes and graphene (21–23); however, such devices are not easy to fabricate and characterize electronically with a statistically significant method. Moreover, there have been no computational studies on such junctions aimed at understanding the relation between charge transport and electrode properties.Here, we measure the conductance of a series of graphite/amine-terminated oligophenyl/Au molecular junctions using the STM-BJ technique (4). We show that the conductance of this series decays exponentially with molecular backbone length with a decay constant that is essentially the same as that for measurements with Au electrodes. We show further that these molecular junctions rectify (14, 24), due to an asymmetry in the coupling of the molecule with the Au and graphite electrodes. The nature and magnitude of the rectification is directly connected to the nonconstant density of states of graphite near the Fermi level. The trends from self-energy–corrected density functional theory calculations are in agreement with our experimental results; specifically, we find that junction conductance decreases as the junction is elongated, as the angle between the molecule and the graphite substrate increases. These measurements and calculations together demonstrate new classes of molecular junctions with dissimilar electrodes using layered 2D electrodes.     

Heliox during mechanical ventilation

The indications for heliox during mechanical ventilation are lower-airway obstruction, especially with hypercarbia; need to enhance aerosol delivery to lung periphery; and need to facilitate weaning from mechanical ventilation. Certain ventilators perform relatively well with heliox and are not substantially affected by it. It is preferable to connect the heliox to the air inlet of the ventilator, because this results in more consistent delivery of oxygen and tidal volume. When administering heliox, pay close attention and directly monitor the actual tidal volume and fraction of inspired oxygen.     

Cardanol Benzoxazines: A Versatile Monomer with Advancing Applications

Polybenzoxazines are evolving as a new class of phenolic resins with a tremendous amount of applications. The ease of structural designing, synthetic procedure, and polymerization reactions are attractive to affect their properties ensuing as an effective substitute for many existing polymers. The nonrenewable origin, toxicity, and increasing cost of petro‐based raw materials are alarming issues. Therefore, the emergence of sustainable benzoxazines, especially based on naturally abundant, agro‐waste origin cardanol is encouraging as it allows both solventless synthesis of monomers and processing to form highly thermally stable thermoset resins. The inherent functionalities in cardanol benzoxazine provide a platform for further structural modifications to advance their applications as adhesives, composites, and energy storage devices.     

Effect of Preparation Taper,Height and Marginal Design Under Varying Occlusal Loading Conditions on Cement Lute Stress: A Three Dimensional Finite Element Analysis

The functional surfaces of the porcelain fused to metal fixed partial dentures are often abraded to adjust occlusion, such restorations are often found to fail in service. This study was therefore conducted to study the effect of surface abrasion on flexural strength of glazed porcelain fused to metal samples. It was also the aim of this study to find the effect of re-glazing on flexural strength of abraded samples. A total of ninety glazed porcelain fused to metal bar samples of the dimension 15 mm × 2 mm × 1.5 mm were fabricated. These samples were then divided into three groups (30 samples each) according to the surface treatments: group A-glazed (control); group B-abraded and group C-abraded and then re-glazed (self-glazed). Flexural strength was measured by using three point bend test on universal testing machine (texture analyser) with a cross-head speed of 0.6 mm/min. Peak force at the time of failure for all the samples was recorded. Statistical analysis found that mean flexural strength was highest for group A-80.65 ± 12.81 MPa; as compared to group B-74.18 ± 10.74 MPa and group C-77.85 ± 9.39 MPa. Student’s t test indicated that the difference in the flexural strength between groups A and B was significant while it was non-significant between groups B and C and also between groups A and C. The ‘f’ test indicated that the difference between the groups was non-significant. This study therefore showed that there is a marked decrease in the flexural strength of the porcelain fused to metal restorations after occlusal abrasion. The study also found that reglazing of these restorations may not restore their flexural strength significantly.